Cancer in Dense Breasts No More Deadly

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High mammographic breast density is not associated with a higher risk of death from breast cancer, a study has found.

Note that high mammographic breast density was not associated with risk of death from any cause after accounting for other patient and tumor characteristics.

Mammographic breast density may be one of the strongest risk factors for developing breast cancer, but it doesn't have an impact on survival, researchers found.

High density had no correlation with risk of breast cancer death after adjustment for other factors (HR 0.92, 95% CI 0.71 to 1.19) in a national registry analysis by Gretchen L. Gierach, PhD, MPH, of the National Cancer Institute (NCI) in Rockville, Md., and colleagues.

Nor was high density linked to all-cause mortality (adjusted HR 0.83, 95% CI 0.68 to 1.02), they reported online in the Journal of the National Cancer Institute.

"Risk factors for the development of breast cancer may not necessarily be the same as factors influencing the risk of death from breast cancer once it has developed," the group wrote.

"It is reassuring that elevated breast density, a prevalent and strong breast cancer risk factor, was not associated with risk of breast cancer death or death from any cause in this large, prospective study."

Prior studies have shown four- to five-fold higher risk of breast cancer in breasts with a higher proportion of fibroglandular tissue that appears opaque on mammography. Masking of breast cancers doesn't entirely explain the link; what does account for it isn't clear.

The researchers examined 9,232 cases of primary invasive breast carcinoma diagnosed from 1996 through 2005 in the U.S. Breast Cancer Surveillance Consortium, an NCI-supported population-based registry of breast imaging facilities.

During the mean follow-up of 6.6 years, 1,795 of the women died, 889 from breast cancer.

Breast cancer deaths, though, weren't significantly more common in the higher-density classifications as ranked by the Breast Imaging Reporting and Data System (BI-RADS) overall (P=0.23 for trend) in the model fully adjusted for site, age at diagnosis, year of diagnosis, cancer stage, body mass index, mode of detection, treatment, and income.

High mammographic density may reflect greater exposure to circulating growth factors, which would tend to boost risk of other types of cancers as well as non-neoplastic diseases, the researchers pointed out.

But in the study, more dense breasts weren't linked to higher risk of death due to any cause (P=0.22 for overall effect).

The hazard ratio of all-cause mortality for women with breast cancer in highly dense breasts classified as BI-RADS 4 was 0.83 compared with those who had BI-RADS 2 density breasts (95% CI 0.68 to 1.02).

The only high breast cancer mortality-risk group appeared to be women with low-density breasts (BI-RADS 1) who were obese or had larger tumors of at least 2.0 cm, with significant hazard ratios of 2.02 and 1.55, respectively.

Prior studies haven't suggested these associations, but it's plausible because "breasts with a higher percentage of fat may contribute to a tumor microenvironment that facilitates cancer growth and progression," Gierach's group wrote.

Breast density might be useful to integrate in clinical trials to see if it aids in identification of women most likely to benefit from targeted treatments or prevention strategies, they suggested.

The investigators acknowledged that BI-RADS classification has only moderate interobserver reliability, so some women may have been misclassified in the study.

Other limitations were the lack of detailed data on treatment, comorbidities, and changes in weight after diagnosis, and the fact that unmeasured confounding couldn't be ruled out.

The study was funded by the National Institutes of Health, the National Cancer Institute (NCI), and the NCI-funded Breast Cancer Surveillance Consortium. No conflict-of-interest information was reported.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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